Hemiballism is a hyperkinetic involuntary movement disorder characterized by intermittent, sudden, violent, involuntary, flinging, or ballistic high amplitude movements involving the ipsilateral arm and leg caused by dysfunction in the central nervous system of the contralateral side. Hemiballism falls as the most severe form within the spectrum of chorea. Chorea is an involuntary movement disorder characterized by brief, sudden, spontaneous, non-stereotyped, and dance-like movements in one side of the body. The classic medical school textbook localizes the lesion to the subthalamic nucleus (STN) or the nucleus hypothalamicus/corpus Luys; however, other research also localizes the lesions in other parts of the basal ganglia and caudate nucleus.
Excessive dopaminergic activity and damage to the pathways of the basal ganglia (hyperkinetic theory) are the basic predominant etiologies of hyperkinetic syndromes. Following are some of the common etiologies of hemiballismus:
Given that chorea syndromes are pathophysiologically a milder spectrum of hemiballismus, etiologies of these have been briefly listed here. Hereditary and primary chorea syndromes can be caused by juvenile and adult-onset, multi-factorial, neurodegenerative, and/or neurodevelopmental disorders such as Huntington disease, Wilson disease, neuroacanthocytosis, dentatorubral-pallidoluysian atrophy, pantothenate kinase-associated neurodegeneration, benign hereditary chorea, paroxysmal choreoathetosis, and senile chorea. Secondary chorea syndromes include metabolic hyperglycemic disorders, dopaminergic drug-induced chorea, Sydenham chorea in acute rheumatic fever in children, Vitamin B1/B12 deficiency, toxic exposure, and post-pump choreoathetosis.
The global incidence and prevalence of ballismus and chorea syndromes are difficult to ascertain and are largely unknown; however, it is estimated to be 1 to 2 per 1,000,000. This categorizes hemiballismus as a rare complication of several disorders, as mentioned above. However, for the interested readers, the epidemiology of hereditary and acquired hyperkinetic syndromes can be found in the literature.
Hemiballimus is a consequence of damage in the basal ganglia structures involved in the inhibitory pathways. With the decreased excitatory transmission of the globus pallidus internus (GPi) and the disinhibition of the thalamus, it creates an overactivation of the corticospinal and corticobulbar tracts with random firing. Subsequently, efferent innervation is sent to muscles on the contralateral side. Intraoperative monitoring studies show decreased firing of cells in the GPi after a pallidotomy, a surgical treatment to decrease hyperkinetic movements. The neurology-neurosurgical team uses the perioperative rate of firing to assess the efficacy of their targeted intervention.
To better understand the pathophysiology of hemiballismus, a review of the complex basal ganglia inhibitory and excitatory pathways is mandatory. The cortex input is generated and sent to the nuclei of the basal ganglia, with a subsequent output directly to the motor neurons in the frontal lobe and brainstem, leading to planned activation or inhibition of movement. The basal ganglia nuclei consist of the caudate, putamen, globus pallidus, STN, and substantia nigra. The fibers from the globus pallidum convert into a white matter tract called the lenticular fasciculus that forms a bundle called the thalamic fasciculus as it enters the thalamus. The latter is an important relayer of excitatory signals to the motor cortex and somatosensory signals coming from the body. Strokes causing hemichorea-hemiballismus usually localizes to a common functional network with lesions occurring in regions functionally connected to the posterolateral putamen, reinforcing the hyperkinetic movement disorder theory.
Given that the large number of disorders that cause hemiballism-hemichorea is exhaustive, it is difficult to mention all the neuropathological findings in this spectrum disorder. A relevant example is hyperglycemia syndrome. A stained anteroposterior coronal section of the basal ganglia can show fibrosis and dilation of small perforating arteries. Within them, there is evidence of macrophage infiltration within the small lacunar infarcts. Other inflammatory findings include protein and iron deposition and astrocytic gliosis. Although the neuropathological findings may vary depending on the etiology of the disease, the commonality between them is the anatomical nuclei and pathways affected within the basal ganglia circuit.
Hemiballismus and hemichorea can present with other symptoms besides the motor involuntary, jerky, large amplitude, irregular, appendicular movements on the contralateral side. For stroke or intracranial hemorrhage, cranial nerve signs can include anisocoria, ptosis, facial droop, dysarthria, and headaches. Patients with neoplasm can become altered and disoriented and may be unable to follow commands. Depending on the size, it causes motor and sensory deficits. For younger patients, neuroinfectious and neuroinflammatory etiologies should be explored, with history screening for risk factors, past neurological events, medical co-morbidities, a thorough sexual, and family history. Food, occupational, and travel history should also be obtained. A good medication reconciliation review can provide clues of any drug-induced hyperkinetic disorder. A thorough neurological examination, including cognitive evaluation, cranial nerve, neck rigidity, motor tone, sensory, balance, and gait exam, could also provide clues in the case of rare disorders underlying the abnormal movements. Information from family members may be necessary to complete the history.
Given the wide variety of disorders that can cause hemiballism, a good medical history and physical evaluation can pinpoint or narrow the diagnosis without requiring any ancillary studies. Old patients with multiple vascular risk factors (e.g., hypertension, diabetes, previous strokes) would need advanced vessel imaging to confirm any hemorrhage or stroke, and if positive, would need a thorough stroke workup.
Thorough routine serum labs, depending on suspected etiology, can include a complete metabolic panel (CMP) and complete blood count (CBC), hemoglobin A1C, serum osmolality, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-nuclear antibody (ANA), extranuclear antibody (ENA), vitamin panel (e.g., B1, B12, etc.), ceruloplasmin, copper level, other heavy metals, drugs of abuse toxicology, HIV antibody screen (if positive opportunistic infection screen), lupus antibodies (C3/C4, double-stranded DNA, anti-histone), antineutrophil cytoplasmic antibodies (ANCA) studies, cryoglobulin, among other immune and infectious markers.
A contrast brain magnetic resonance imaging (MRI), computed tomography angiogram (CTA), magnetic resonance angiography (MRA), or digital subtraction angiogram (DSA) may be used to evaluate for autoimmune pathology, structural abnormalities, or malignancy.
If neuroinfectious (opportunistic bacterial, viral-HIV, or fungal-toxoplasmosis) or neuroinflammatory/paraneoplastic etiology is suspected, a lumbar puncture with extensive cerebrospinal fluid (CSF) basic and advanced studies (oligoclonal bands, CSF index), including flow cytology and cytometry should be obtained. Genetic studies should be sent when indicated, and there is a strong clinical suspicion for a hereditary etiology.
Treating the underlying etiology is important, as hemiballismus tends to resolve with time. Therefore, supportive treatment for comorbidities and related complications is important.
Medical management includes the use of first and second-generation antidopaminergic drugs, to target D2 receptors (e.g. risperidone, haloperidol, perphenazine, pimozide, chlorpromazine), benzodiazepines (clonazepam), anti-epileptics (topiramate), and tetrabenazine to relieve severe hyperkinetic movements.
If patients become refractory to medical management, and the symptoms are severe enough to impair activities of daily living, surgery becomes an option. A stereotactic posteroventral pallidotomy is the procedure of choice and leads to decreased firing of pallidal neurons, leading to relief of the hyperkinetic movements. Micro-recording and intraoperative monitoring are performed during surgery to improve targeted accuracy during the procedure. Intrathecal baclofen has also shown results with post-traumatic hemiballismus. Deep brain stimulation has not been recommended.
Hemiballistic movements should not be confused with other hyperkinetic movements. Given that hemiballismus and chorea are within a spectrum of hyperkinetic disorders, the history, and physical exam will help you narrow the diagnosis and guide the neurologist to order the appropriate ancillary testing, which includes comprehensive serum testing, brain imaging, and at times CSF studies. It is important to tease out the different disorders presenting with hemiballismus.
Hemiballismus usually has a good prognosis with remission of symptoms within a few weeks after commencing treatment for those treatable conditions. Unresponsive cases can require surgical intervention.
Complications from the treatment are rare given hemiballismus is a consequence of damage to the inhibitory pathways in the basal ganglia, and it tends to self-resolve over time with symptomatic treatment. Treating the underlying etiology, especially in acute life-threatening etiologies like an ischemic stroke, is key to avoid further complications and functional deterioration.
As hemiballismus can be caused by multiple diseases, it requires interprofessional evaluation and management for promising outcomes. The following are the consultations that may be needed in the management of the underlying disorder.
Patients should understand that the causes for hemiballismus may vary depending on the underlying disorder associated with it. Any of the following disorders may present with hemiballismus: traumatic brain injury, stroke, cancer, metabolic, systemic infections, brain infections, autoimmune diseases, genetic disorders, medication side effects, vitamin deficiencies, and toxic substance exposure. Treating the underlying etiology is extremely important. Medical treatment for hyperkinetic movements is sometimes recommended, but surgery is rarely used. Patients should be encouraged that hemiballismus tends to resolve with time. Consultation with the social worker and the psychologist is usually necessary due to the emotional effect that hemiballismus may cause on these patients.
Additional Patient Resources
Hemiballismus has a good prognosis with symptomatic and pharmacological treatment, as long as the underlying disorder is addressed. In the case of noncurative etiologies, such as seen in neurodevelopmental, neoplastic, and neurodegenerative disorders, an interdisciplinary team of primary care, specialists and subspecialty physicians (general neurology, neurosurgery, movement disorder, neuroimmunology specialist, genetics, oncology, infectious disease, rheumatology, palliative care, social workers, physical/occupational/speech therapists, behavioral health) should work together to coordinate care in accordance to patient-centered goals of care. Particularly in the case of hereditary disorders, genetic counseling to the patient and family members is essential. [Level 5]
|||Grandas F, Hemiballismus. Handbook of clinical neurology. 2011; [PubMed PMID: 21496584]|
|||Laganiere S,Boes AD,Fox MD, Network localization of hemichorea-hemiballismus. Neurology. 2016 Jun 7; [PubMed PMID: 27170566]|
|||Postuma RB,Lang AE, Hemiballism: revisiting a classic disorder. The Lancet. Neurology. 2003 Nov; [PubMed PMID: 14572734]|
|||Noda K,Hattori N,Okuma Y, Hemiballism with leg predominance caused by contralateral subthalamic haemorrhage. BMJ case reports. 2015 Apr 9; [PubMed PMID: 25858962]|
|||Jaafar J,Rahman RA,Draman N,Yunus NA, Hemiballismus in Uncontrolled Diabetes Mellitus. Korean journal of family medicine. 2018 May; [PubMed PMID: 29788710]|
|||Ozer F,Meral H,Aydemir T,Ozturk O, Hemiballism-Hemichorea in presentation of cranial tuberculoma. Movement disorders : official journal of the Movement Disorder Society. 2006 Aug; [PubMed PMID: 16700030]|
|||Deuschl G, Movement disorders in multiple sclerosis and their treatment. Neurodegenerative disease management. 2016 Dec; [PubMed PMID: 27874491]|
|||Cross SA,Salomao DR,Parisi JE,Kryzer TJ,Bradley EA,Mines JA,Lam BL,Lennon VA, Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG. Annals of neurology. 2003 Jul; [PubMed PMID: 12838519]|
|||Athanasopoulos E,Kalaitzidou I,Vlachaki G,Stefanaki S,Tzagkaraki A,Niotakis G,Tritou I,Ladomenou F, Chorea revealing systemic lupus erythematosus in a 13-year old boy: A case report and short review of the literature. International reviews of immunology. 2018; [PubMed PMID: 29595356]|
|||Termsarasab P, Chorea. Continuum (Minneapolis, Minn.). 2019 Aug; [PubMed PMID: 31356291]|
|||McColgan P,Tabrizi SJ, Huntington's disease: a clinical review. European journal of neurology. 2018 Jan; [PubMed PMID: 28817209]|
|||Kırık S,Güngör O,Kırık Y, Importance of Streptococci Infections in Childhood Neuropsychiatric Disorders. Sisli Etfal Hastanesi tip bulteni. 2019; [PubMed PMID: 32377124]|
|||Natera-Villalba E,Estévez-Fraga C,Sánchez-Herrera FA,Ruiz-Gómez F,Sanz BZ,Cánovas AA,Martínez-Castrillo JC,Corral ÍC, Simultaneous acute presentation of generalized chorea and subacute combined degeneration secondary to vitamin B12 deficiency. Parkinsonism [PubMed PMID: 30220555]|
|||Sabatini JS,Schutz-Pereira GL,Feltrin F,Teive HAG,Camargo CHF, Wernicke's encephalopathy with chorea: Neuroimaging findings. Dementia [PubMed PMID: 29213485]|
|||Miyasaki JM, Chorea caused by toxins. Handbook of clinical neurology. 2011; [PubMed PMID: 21496593]|
|||Jamra DA, Neurologic outcomes in children with post-pump choreoathetosis. Pediatric physical therapy : the official publication of the Section on Pediatrics of the American Physical Therapy Association. 2002 Fall; [PubMed PMID: 17053699]|
|||Holden KR,Sessions JC,Curé J,Whitcomb DS,Sade RM, Neurologic outcomes in children with post-pump choreoathetosis. The Journal of pediatrics. 1998 Jan; [PubMed PMID: 9470021]|
|||Mestre T,Ferreira J,Pimentel J, Putaminal petechial haemorrhage as the cause of non-ketotic hyperglycaemic chorea: a neuropathological case correlated with MRI findings. BMJ case reports. 2009; [PubMed PMID: 21686632]|
|||Cheema H,Federman D,Kam A, Hemichorea-hemiballismus in non-ketotic hyperglycaemia. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2011 Feb; [PubMed PMID: 21159513]|
|||Evidente VG,Gwinn-Hardy K,Caviness JN,Alder CH, Risperidone is effective in severe hemichorea/hemiballismus. Movement disorders : official journal of the Movement Disorder Society. 1999 Mar; [PubMed PMID: 10091643]|
|||Johnson WG,Fahn S, Treatment of vascular hemichorea and hemiballismus with perphenazine. Transactions of the American Neurological Association. 1974; [PubMed PMID: 4618686]|
|||Zheng W,Chen L,Chen JH,Lin X,Tang Y,Lin XJ,Wu J,Lin ZM,Lin JY, Hemichorea Associated With Non-ketotic Hyperglycemia: A Case Report and Literature Review. Frontiers in neurology. 2020; [PubMed PMID: 32158423]|
|||Xiao F,Liu M,Wang XF, Involuntary choreiform movements in a diabetic patient. Lancet (London, England). 2019 Mar 9; [PubMed PMID: 30860028]|
|||Driver-Dunckley E,Evidente VG, Hemichorea-hemiballismus may respond to topiramate. Clinical neuropharmacology. 2005 May-Jun; [PubMed PMID: 15965315]|
|||Sitburana O,Ondo WG, Tetrabenazine for hyperglycemic-induced hemichorea-hemiballismus. Movement disorders : official journal of the Movement Disorder Society. 2006 Nov; [PubMed PMID: 16986158]|
|||Kenney C,Jankovic J, Tetrabenazine in the treatment of hyperkinetic movement disorders. Expert review of neurotherapeutics. 2006 Jan; [PubMed PMID: 16466307]|
|||Francisco GE, Successful treatment of posttraumatic hemiballismus with intrathecal baclofen therapy. American journal of physical medicine [PubMed PMID: 16924190]|